Is educational attainment associated with the onset and outcomes of low back pain? a systematic review and meta-analysis

Background Low back pain (LBP) is the leading global cause of years lived with disability. Of the biopsychosocial domains of health, social determinants of LBP remain under-researched. Socioeconomic status (SES) may be associated with the onset of new LBP or outcomes of acute LBP, with educational attainment (EA) being a key component of SES. The association between EA and LBP has yet to be the subject of a dedicated review and meta-analysis. Purpose To review evidence of the association between EA and a) onset or b) outcomes of acute and subacute LBP in the adult general population and to conduct statistical pooling of data where possible. Methods An electronic search was conducted in MEDLINE, Embase, CINAHL, and ProQuest from inception to 2nd November 2023 including reference lists to identify relevant prospective studies. Risk of bias (RoB) was assessed using the Quality in Prognostic Studies (QUIPS) tool. Where adequate data were available, estimates were pooled using a random-effects meta-analysis. Overall evidence for each outcome was graded using an adapted GRADE. Results After screening 8498 studies, 29 were included in the review. Study confounding and attrition were common biases. Data from 19 studies were statistically pooled to explore EA as a predictor of new LBP onset or as prognostic for outcomes of acute or subacute LBP. Pooled results showed no association between EA and the onset of new LBP (OR: 0.927, 95%CI: 0.747 to 1.150; I2 = 0%). For predicting outcomes of acute LBP, compared to those with no more than secondary-level education, post-secondary education or higher was associated with better outcomes of pain (OR: 0.538, 95%CI: 0.432 to 0.671; I2 = 35%) or disability (OR: 0.565, 95%CI: 0.420 to 0.759; I2 = 44%). High heterogeneity (I2>80%) prevented meaningful pooling of estimates for subacute LBP outcomes. Conclusion We found no consistent evidence that lower EA increases the risk of LBP onset. Lower EA shows a consistent association with worse LBP outcomes measured at least 3 months later after acute onset with inconclusive findings in subacute LBP. Causation cannot be supported owing to study designs. High-quality research is needed on potential mechanisms to explain these effects.

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No ethics approval is required for this study.Methods: An electronic search was conducted in MEDLINE, Embase, CINAHL, and ProQuest from inception to 2 nd November 2023 including reference lists to identify relevant prospective studies.Risk of bias (RoB) was assessed using the Quality in Prognostic Studies (QUIPS) tool.Where adequate data were available, estimates were pooled using a randomeffects meta-analysis.Overall evidence for each outcome was graded using an adapted GRADE.

Results:
After screening 8498 studies, 29 were included in the review.Study confounding and attrition were common biases.Data from 21 studies were statistically pooled to explore EA as a predictor of new LBP onset or as prognostic for outcomes of acute or subacute LBP.Pooled results showed no association between EA and the onset of new LBP (OR: 0.927, 95%CI: 0.747 to 1.150; I 2 = 0%).For predicting outcomes of acute LBP, compared to those with no more than secondary -level education, post-secondary education or higher was associated with better outcomes of pain (OR: 0.538, 95%CI: 0.432 to 0.671; I 2 = 35%) or disability (OR: 0.565, 95%CI: 0.420 to 0.759; I 2 = 44%).High heterogeneity (I 2 >80%) prevented meaningful pooling of estimates for subacute LBP outcomes.

INTRODUCTION
Low back pain (LBP) is a leading global cause of years lived with disability. 1 In North America, chronic LBP is amongst the top ten reasons for seeking medical attention 2 with a prevalence of 18-23% in adults Canadians. 3While many LBP cases resolve within the first three months, it has been estimated that as many as 60% to 80% progresses to chronicity or recurrence within one year including loss of productivity in 40%. 4,57][8] Prevention of new LBP or prevention of the acute-tochronic transition stand to have major impact on global health burden. 2 Existing guidelines recommend early identification of psychosocial factors that could prevent or enhance recovery from LBP. 9 While the biological and psychological sciences have provided considerable evidence to explain onset of and recovery from LBP, much less attention has been paid to the social influences.Social determinants of health (SDOH) are increasingly recognized as potent influences on the genesis of several health states, 10 with some prior authors indicating that neighborhood characteristics may have at least as large an influence on the experience of chronic diseases as do personal genetics. 11While SDOHs represent a large and complicated field of research, there are some social variables unique to the person experiencing pain that are worthy of dedicated inquiry.One such variable is educational attainment (EA), defined as the highest level of education completed by a person.As a prognostic variable, EA represents a blend of person-level (e.g., literacy) and society-level (e.g., access) influences and could potentially hold value as a variable through which intervention strategies could be tailored.EA holds value for research on SDOHs as "years of education" is one of few such variables that can be readily quantified.
There is some evidence that chronic pain is more prevalent amongst people with low EA 12 and lower EA may predict the acute-to-chronic transition. 13However, there are limited studies that focus solely on the social predictors of LBP specifically. 6EA has been included in some prior systematic reviews in LBP 14,15 though differences in case definitions, variable definitions, or study design have precluded clear findings.Even rarer are reviews or evidence syntheses on the association between EA and the onset of new LBP in population-level cohort studies that start with pain-free participants. 16If lower EA is a risk for new onset LBP or for poor recovery following onset of acute LBP, mechanisms could then be explored and if causation is supported EA could be integrated into either public health prevention strategies or tailored treatment planning to prevent the acute-to-chronic transition.
The purpose of this systematic review was to qualitatively and/or quantitatively synthesize published estimates on the risk and prognostic value of EA on the onset or outcomes of LBP.

Design
This review was designed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework.The review was limited to observational prospective cohort or population-level studies (not clinical trials) of patients aged >18 years with either no LBP at inception (followed to determine onset), or acute (<8 weeks) and/or sub-acute (8-12 weeks) LBP.We focused on 'non-specific' LBP and therefore excluded LBP related to underlying systemic medical (such as cancer, infection, or cauda equina syndrome), vertebral compression fracture or osteoporosis, inflammatory conditions (e.g., ankylosing spondylitis) or neurological conditions (e.g., stroke).Beyond that, we accepted the case definitions of LBP as reported by the authors of the primary sources.

Search Strategy
The search strategy (Appendix A) was developed with a research librarian using MeSH terms specific to MEDLINE which was adapted for other databases.No specific restrictions on publication date were set.The search strategies were applied to MEDLINE (OVID), The Cumulative Index of Nursing and Allied Health Literature (CINAHL), EMBASE, and ProQuest from inception to 30 th March 2023 and updated to 2 nd November 2023 corresponding to the dates of the respective searches.A grey literature search of unpublished studies was conducted in Researchsquare.Hand searches of reference lists of all included articles were conducted to identify additional primary sources.

Study Selection
Yield from each database were imported into Covidence systematic review software (Veritas Health Innovation, Melbourne Australia) and screened by two independent reviewers against the inclusion criteria, with disagreements being resolved by a third reviewer.Titles and abstracts were screened to remove clearly irrelevant sources, followed by full text screening against the inclusion/exclusion criteria.Kappa was calculated as an indicator of agreement between raters.The reasons for exclusion are included in Figure 1.

Risk of bias in individual studies
The Quality in Prognostic Studies (QUIPS) tool was used to assess RoB of all included studies.QUIPS consists of six category-domains of potential biases: i) study participation, ii) attrition, iii) prognostic factor measurement, iv) outcome measurement, v) confounding, and vi) statistical analysis / reporting.All included studies were assessed by 2 independent reviewers.We used a worst-score approach, where each paper was assigned a RoB based on the worst (highest risk) rating of any of the 6 categories 17 classed as low, moderate, or high risk of bias (RoB).RoB agreement was calculated through Cohen's kappa with disagreements resolved through discussion with a third experienced reviewer.

Data Extraction
Data were extracted using a study-specific extraction table that included key study descriptors, sample characteristics, operationalizations of EA and LBP, outcomes assessed, and relevant findings.Educational attainment was extracted with as much detail as reported in the publication.Where possible, the minimum data extracted were related to a 12-year cut-point for EA as representing the threshold between secondary (up to year 12) and post-secondary (beyond year 12) EA in most countries.Where data were not presented with adequate detail, EA was sorted into meaningful order based on the manner reported in the studies (e.g., low vs high).We did not restrict studies based on the length of follow-up but extracted that information for subsequent interpretation as a potential effect modifier.
Outcomes were limited to those broadly categorized as either pain (e.g., presence/absence of LBP or pain intensity) or disability (e.g., return to work or score on a standardized patientreported outcome).Where studies reported "recovery" as an outcome those operationalizations were reviewed for relevance and if aligned with our purpose the verbatim definition was extracted and assigned to the most relevant outcome category (e.g., pain, disability, or both).
The study protocol was prospectively registered in PROSPERO (registration no.CRD 42023402135) as part of a series of reviews on SDOHs and LBP.

Data analysis and synthesis
Where possible, data were pooled and presented as odd ratio through random-effects metaanalysis using Comprehensive Meta-analysis software, version 2.2.04 (Biostat, Inc.©, Englewood, New Jersey).Syntheses were conducted for each of: i) onset of LBP (inception cohorts that start with no LBP and are followed over time to identify those who later report LBP); ii) pain intensity outcomes in acute LBP (inception starting within 8 weeks of LBP onset and followed over time to evaluate recovery), iii) pain-related disability outcomes in acute LBP, and iv) pain or disability outcomes in those entering the study with subacute (8 to 12 weeks) LBP.Heterogeneity in effects was assessed using both the Chi-squared test (p-value) and the I-squared statistic.I-squared <30% was deemed low heterogeneity, 30-60% as moderate, 61-75% as substantial, and 76-100% as considerable heterogeneity. 18First, one estimates for pain and/or disability were pooled for unadjusted from each study and where the unadjusted is not available, the adjusted is pooled.Where substantial or considerable heterogeneity was identified, and where enough primary sources were available, sensitivity analysis was undertaken to explore potential sources of heterogeneity by pooling only the unadjusted estimates in each study.
When heterogeneity could not be explained, or where there were too few primary sources to permit moderator analysis in otherwise highly heterogeneous effects, a narrative summary of the results is presented.

GRADE assessment
Results across studies were synthesized using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach that considered the strength of the effect (none, small, medium, or high) and confidence in the results (inconclusive, low, moderate, or high) based on RoB, precision, homogeneity and consistency of effects.Where effects could be statistically pooled, those results were used to determine effect size, where they could not, we used a qualitative synthesis approach focused on overall consistency across papers.For this review, we did not attempt to find study registration through online registries to identify publication bias as observational studies are not consistently registered and many studies were published prior to protocol registration becoming standard practice.

RESULTS
Figure 1 shows the PRISMA flow diagram.The search identified 8498 articles (including 1058 duplicates), of which 163 full texts were screened resulting in the inclusion of 23 articles.An additional 4 from reference lists and 2 from the update search were identified for a total of 29 manuscripts describing 27 prospective observational cohorts.The average agreement between raters was Kappa = 0.54, and random agreement was 0.97.Characteristics of the included studies are summarized in Table 1.The included studies were grouped into: onset of new LBP (n=3), outcome of acute LBP (n=18) and outcome of subacute LBP (n=8).The publication date of the included studies spanned 1991 to 2022 and were from 13 countries.Sample sizes ranged from 53 19 to 12,500 20 and follow-up periods from 3 months (n = 4 [21][22][23][24] ) to 3 years (n = 2 20,25 ).

Risk of Bias
Details of the RoB are reported in Table 1 and RoB for the overall body of literature is presented in Figure 2. The majority (n = 14) of the included studies were rated as high RoB with 13 rated moderate and 2 low.For the individual domains, low RoB was common in the domains of study participation (77%) and statistical analysis/reporting (74%).High RoB was common for the domains of confounding (45%) and study attrition (39%).

Prognostic factors
Operational definitions and categories of EA were defined differently across studies.Thirteen studies 20,21,23,25,27,28,30,31,33,36,37,39,42 had EA according to a 12-year education grade (e.g., 12 years or less, 12 years or more).Three did not present adequate data for extracting years of education.Silva et al 35 categorized education as 'low, medium, or high" with no specific details, and Valencia et al 41 combined income and education into a single index of socioeconomic status.Turner et al 40 reported EA as highest grade of education completed without detailing the years.

Outcomes
Outcomes were broadly categorized into pain, disability or a combination of pain and disability.
Pain was evaluated using 21 outcomes across 14 studies with the Numeric Pain Rating Scale (NPRS), 28,35,39,41,42 and Visual Analog Scale (VAS) 44 the most frequent.Disability was evaluated using 21 outcomes in 9 studies most commonly using the Oswestry Disability Index (ODI) 19,41,47 and Roland Morris Disability Questionnaire (RMDQ). 22,28,35A combination of both pain and disability was evaluated in two studies. 22,31
EA as a predictor for the onset of new LBP Figure 3 show the forest plot for pooled estimate for the association between EA and the onset of LBP.Three longitudinal inception cohort studies [25][26][27] (total N = 3,110) presented adequate data for pooling.The pooled effect of the three studies shows consistent evidence of no association between EA and new onset of LBP (OR = 0.93; 95%CI 0.75 to 1.15) with homogeneity (I 2 < 0.1%).EA as a prognostic variable for predicting outcome of acute LBP.
Eight studies (total N = 15,079) reporting pain as an outcome were pooled with low-moderate heterogeneity in effect sizes (I 2 = 35%).Results supported a significant effect, in which higher EA predicts lower intensity LBP symptoms 3 months to 3 years after onset of acute LBP (OR = 0.54; 95%CI 0.44 to 0.67, Figure 3).Three of those studies reported adjusted estimates only, excluding those resulted in an equivocal shift in pooled effects using only the unadjusted estimates (OR = OR: 0.51, 95%CI: 0.37 to 0.70, I = 36%, Figure 4).Nine articles (8 cohorts, total N = 4,672 subjects) reported a pain-related disability outcome.Pooling similarly indicated that higher EA measured in the acute phase of LBP predicts lower pain-related disability 3 months to 12 months later (OR = 0.57; 95%CI 0.42 to 0.76, Figure 3) with moderate heterogeneity (I 2 = 44%).Excluding the adjusted estimates from two of those studies again resulted in an equivocal shift in pooled effect (OR: 0.62, 95%CI: 0.51 to 0.77, Figure 4) but without heterogeneity (I 2 = 0%).Of the three studies that could not be pooled, two studies 24,38 (moderate RoB, total N = 1,369) also reported significant associations between outcomes of acute LBP and EA.The third 32 (1 moderate RoB, N = 55 subjects) reported no association between EA and disabling LBP/time to return to work.EA as a prognostic variable for predicting outcome of subacute LBP.
Two (pain severity) 23,41 and three (pain-related disability) 19,41,42 studies predicting outcomes in subacute LBP could not be meaningfully pooled owing to high heterogeneity (I 2 > 79%), inconsistent outcomes, and too few sources to permit moderator analysis.Accordingly, we proceeded with qualitative synthesis.For pain intensity as an outcome 4 of 6 studies (2 low 43,44 and 2 moderate 23,45 RoB, total N= 2,880) reported unadjusted (bivariate) estimates and indicated no association between EA and follow-up outcome.The remaining two studies (1 low 47 and 1 moderate 41 RoB, total N= 272) reported no significant association after adjusting for pain catastrophizing 41 or age, gender, occupation, health status. 47For pain-related disability, 7 studies (1 low, 3 moderate and 2 high RoB studies, total N = 1,960) reported inconsistent evidence.Two studies 42,46 (total N = 1,504) found a significant negative association between EA and pain-related disability as measured with the RDQ 42 and ability to return to work 46 .Four other studies 42,44 (2 low, 19,47 1 moderate 19 and 1 high 41 RoB, total N = 403) reported no association between EA and ODI 19,41,47 or sickness profile. 43based analysis of educational attainment and low back pain outcomes.
Two studies analyzed data for potential differential effects of EA on LBP when disaggregated by sex.The two studies could not be pooled due to differences in case definitions.Zadro et al 26 studied new onset LBP and reported lower EA to be associated with increased proportion of new onset LBP in females only, with no significant effects in males.Sterud et al 20 evaluated outcomes in acute LBP and found no differential effect on outcome between sexes.

GRADE STATEMENT
Evidence profile of all included studies applied using GRADE is presented table 2.
EA and onset of LBP: On the basis of 3 studies, 1 moderate and 2 high RoB, with consistency in magnitude of effect, we find low-to-moderate confidence that EA has no association with onset of new LBP in adults when followed for at least 2 years.
EA and outcomes of acute LBP: On the basis of 9 of 11 studies, 6 moderate and 3 high RoB, we have moderate confidence that EA when collected at inception shows a significant association with LBP symptom severity measured at least 3 months later.We find low confidence based on 5 of 11 studies, 2 moderate and 3 high RoB of a similar association when the outcome is pain-related disability.
EA and outcomes of subacute LBP: On the basis of 7 of 9 studies, 2 low, 3 moderate, and 2 high RoB, we find inconsistent evidence and very low confidence on any association between EA and subsequent outcomes of pain severity when participants are incepted at the subacute (8-12 weeks from onset) stage.We find inconsistent evidence based on 3 of 5 studies (1 low, moderate and high RoB) and very low confidence for no association between EA and disability at least 3 months later.Significant heterogeneity in case definitions and effect sizes preclude more definitive findings.

Discussion
We have conducted a rigorous and systematic search, extraction, and pooling of effects to explore the associations between a key indicator of socioeconomic status (highest level of education completed) and each of onset of new LBP, outcomes of acute LBP, or outcomes of subacute LBP.This represents part of an ongoing set of reviews exploring the social determinants of health and their associations with LBP, conceptualized herein as evaluating whether lower EA (high school or less) functions as either a potential risk or prognostic factor for onset or outcome of LBP, respectively.As observational studies these are inherently vulnerable to confounding bias from several other potential variables meaning causation should not be assumed.Based on the strength and effects of available evidence, we have moderate confidence in a significant negative association between EA and pain severity or disability outcomes of acute LBP in which higher EA may offer some protection against poor outcomes, low confidence that EA has no association with onset of new LBP, and very low confidence of any association between EA and outcome when starting from the subacute LBP stage.
While to our knowledge the synthesis of evidence related to new-onset LBP is novel, our results are largely consistent with those of other reviews in acute or subacute LBP, each of which included EA as part of a larger set of potential prognostic variables and few of which conducted meta-analyses.Previous LBP studies have failed to establish an association between EA and LBP outcomes for various reasons such as a small sample size to statistically power the study to detect effects, 42 lack of uniform study design, 48 and heterogeneous population, among others.For example, a review by Batista et al 48 reported that individuals with higher EA are less often affected by the occurrence of LBP.However, that review included multiple study designs that might have added noise to any estimates of effect.Cancelliere and colleagues 49 based on best evidence synthesis of systematic reviews on factors affecting return to work after injury or illness identified higher EA and socioeconomic status among factors associated with positive return-to-work outcomes.A similar review by Dionne and colleagues 50 included multiple study designs that could not allow establish prediction or causation, though that review concluded that people with lower EA are more likely to be affected by disabling LBP.
While it is tempting to ascribe mechanisms to either the finding of no association with onset or consistent association with outcome in LBP, any such attempt is necessarily speculative given the design of studies and the inability to feasibly conduct a randomized trial in which one arm remains uneducated.Accordingly, criteria to support cause-and-effect, most famously described by Bradford-Hill 51,52 may never be fully realized.However, it also limits the impact of this work if no potential mechanisms are explored.EA is commonly included as part of the indices used to assign people to socioeconomic strata, 53,54 that also include variables such as annual household income and median neighborhood income.From a Bourdieusian perspective, each of these may be interpreted as inferring capital that can be converted to power across different social fields. 55In the context of outcomes of LBP, possessing this type of social capital may permit easier access to effective care or alternative employment options for those of SES, meaning that research using outcomes such as work status may find those with economic or educational privilege have better outcomes.However, EA may be functioning more as a proxy for other influences on experiences of health and wellness outcomes.For example, higher EA may also signal higher health literacy, living in more affluent areas with easier access to schools, or family wealth.Lower EA may be associated with, amongst other things, experiences of school bullying, early parentification, poor mental health, or neighborhood poverty. 56Each may also play a moderating or mediating role on health outcomes, 57 suggesting that these effects are very likely complex interactions between person-and society-level influences.
That EA showed no significant association with the onset of new LBP also demands further interpretation.Importantly, on the basis of only 3 studies of moderate-to-high RoB we cannot have more than low confidence in the finding, though the consistency from over 3,000 participants suggests a signal may be present.Intuitively we might expect that those with lower EA are also more likely to be in jobs that demand higher physical labour or more repetitive tasks that might increase the risk of musculoskeletal disorders like LBP.However, we can see prior evidence that appears to support the lack of association identified herein.For example, in a large population-level study of >74,000 U.S. adults aged 30-49, Zajacova and colleagues found a non-linear association between EA and pain, in which adults who started but did not finish a post-secondary educational program reported higher prevalence of painful conditions than either those with completed post-secondary education or those with secondary education only. 58There is also an abundance of evidence associating sedentariness or prolonged sitting, as may be more likely experienced by those with higher-level or managerial roles, as risk factors for low back pain.Further, amongst blue collar workers Lagersted-Olsen and colleagues found no association between daily time spent in a forward-bending posture and onset or aggravation of LBP over one year. 59Accordingly, similar to our commentary on EA and LBP outcomes, any association between EA and LBP onset is likely similarly complex and it seems overly simplistic to suggest that lower education does or does not lead to LBP.
Limitations to the study include the inability to establish causation as previously described, though this is more a limitation of the overall field rather than this particular review.We were also unable to retrieve missing or under-reported data by contacting authors, meaning that some potentially relevant data have not been included in the meta-analyses that may otherwise change the results.All of the included studies were written in English or had a professional English translation available, meaning we may have missed data from work published in non-English journals.Finally, despite our best efforts not all studies reported EA in a way that permitted easy dichotomization into the 12-year categories.We made our best estimates when based on reporting in the manuscript when grouping results into one of these two categories, though acknowledge that some errors may have been made.
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Figure 2 :
Figure 2: Percentage distribution of the types of bias in the quality appraisal criteria of

Fig. 3 .
Fig. 3. Forest plot of prognostic accuracy (odds ratio, OR) of educational attainment for

Fig. 4 .
Fig. 4. Forest plot of the association of unadjusted back pain outcomes (acute and